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Mononuclear Fe(iii) complexes containing an antipyrine Schiff base ligand were prepared and fully characterized, demonstrating a planar tetradentate coordination geometry. The resulting complexes are active for HER with possible ligand cooperativity. 

ABSTRACT Systemic infections byCandidaspp. are associated with high mortality rates, partly due to limitations in current antifungals, highlighting the need for novel drugs and drug targets. The fungal phosphatidylserine synthase, Cho1, fromCandida albicansis a logical antifungal drug target due to its importance in virulence, absence in the host, and conservation among fungal pathogens. Inhibitors of Cho1 could serve as lead compounds for drug development, so we developed a target-based screen for inhibitors of purified Cho1. This enzyme condenses serine and cytidyldiphosphate-diacylglycerol (CDP-DAG) into phosphatidylserine (PS) and releases cytidylmonophosphate (CMP). Accordingly, we developed anin vitronucleotidase-coupled malachite-green-based high throughput assay for purifiedC. albicansCho1 that monitors CMP production as a proxy for PS synthesis. Over 7,300 molecules curated from repurposing chemical libraries were interrogated in primary and dose-responsivity assays using this platform. The screen had a promising averageZ’ score of ~0.8, and seven compounds were identified that inhibit Cho1. Three of these, ebselen, LOC14, and CBR-5884, exhibited antifungal effects againstC. albicanscells, with fungicidal inhibition by ebselen and fungistatic inhibition by LOC14 and CBR-5884. Only CBR-5884 showed evidence of disruptingin vivoCho1 function by inducing phenotypes consistent with thecho1∆∆mutant, including a reduction of cellular PS levels. Kinetics curves and computational docking indicate that CBR-5884 competes with serine for binding to Cho1 with aK_iof 1,550 ± 245.6 nM. Thus, this compound has the potential for development into an antifungal compound. IMPORTANCEFungal phosphatidylserine synthase (Cho1) is a logical antifungal target due to its crucial role in the virulence and viability of various fungal pathogens, and since it is absent in humans, drugs targeted at Cho1 are less likely to cause toxicity in patients. Using fungal Cho1 as a model, there have been two unsuccessful attempts to discover inhibitors for Cho1 homologs in whole-cell screens prior to this study. The compounds identified in these attempts do not act directly on the protein, resulting in the absence of known Cho1 inhibitors. The significance of our research is that we developed a high-throughput target-based assay and identified the first Cho1 inhibitor, CBR-5884, which acts both on the purified protein and its function in the cell. This molecule acts as a competitive inhibitor with aK_ivalue of 1,550 ± 245.6 nM and, thus, has the potential for development into a new class of antifungals targeting PS synthase. 

For 2 weeks in the summer of 2018, K-12 science, technology, engineering, and mathematics (STEM) teachers ( n = 40) attended a professional development (PD) that included four sessions focused on computer science modeling with follow-up academic year sessions; however, overall, the teachers did not incorporate or utilize modeling means or how as the instructors intended. The purpose of the study is to examine why this occurred, and the authors looked at the teachers’ modeling discourse. Using two theories to connect to practice (terministic screens, and schema theory), the authors collected data via the surveys, interviews, and email reflections. The authors analyzed the results via coding to explore participants’ concept of models and the potential difficulties of implementing computer modeling in their classrooms. Findings show that the term model was interpreted differently by the PD’s faculty team and participants. Further, the authors found that the majority of presenters held differing theories of models than the participants. Participant concepts of models did improve slightly after the PD, but lingering model concepts caused confusion with the anticipated PD results. Conclusions include five general modeling concepts which are presented and explained. Implications are provided showcasing articulated keys for delivering PD that assists in eliminating discursive and theoretical issues. Included are considerations for STEM teacher educators, PD providers, and K-12 teachers. The main study limitations include mixed K-12 teaching participants, distance between participants, a self-selected population, and non-generalizable findings based on qualitative work. Future directions are outlined. 

This article explores technology’s integration, assessment, and reflection within a single secondary education program at a Mountain West university. In light of the publication of the Teacher Education Technology Competencies (TETCs), faculty members of a secondary education program focused on existing practices and pathways for expansion to better align with the TETC standards in the future. The purpose of this study was to explore existing practices of incorporating technology into secondary methods coursework and to search for new spaces to implement the TETC guidelines and structure, as well as explore the roles faculty play in the adoption and implementation of technologies. Vignettes authored by faculty in each content area provide a rich depth of faculty experience and dispositions regarding technology integration, as well as spaces for the deeper use of technology based on the TETC recommendations. Key questions emerged about the efficacy of current technology practices, as well as the experiences and dispositions of the faculty within the secondary education program. Findings show that secondary education faculty use domain/content-specific technologies in their course; are expected to be “meta-experts”, both discovering and implementing technology simultaneously; and tend to discover technologies through content-specific interactions and discussions.